Signaling Bone Formation

Improvements in mass spectrometry now allow global quantitation of phosphorylated proteins from cultured cells and comparison of signaling networks. Kratchmarova et al. immunoprecipitated tyrosine phosphorylated proteins (and associated proteins) and determined the relative abundance of peptides in the mixture to characterize the spectrum of signals initiated by two related receptor tyrosine kinases--the epidermal growth factor (EGF) receptor and the platelet-derived growth factor (PDGF) receptor. Human mesenchymal stem cells were induced to differentiate into bone-forming cells by EGF but not by PDGF, and comparison of the two signaling networks revealed that the PDGF activated the phosphatidylinositol 3-kinase (PI3K) pathway, whereas EGF did not. When the PI3K pathway was inhibited, PDGF could promote bone differentiation as effectively as EGF.